In sensory neurons of the eye and inner ear the neurotransmitter, glutamate, is released at active zones in a graded and continuous manner. In these neurons specialized structures have evolved, known as synaptic ribbons. Synaptic ribbons are osmiophilic proteinaceous structures that tether synaptic vesicles near active zones. Because of their morphology, location within the cells and the cell types where they are found, these organelles are undoubtedly important for the continuous release of glutamate; how ribbons aid in this task, however, remains unclear. The focus of this grant is to study the role of synaptic ribbons in sensory synaptic transmission, with the long term goal to resolve the temporal sequence of molecular and cellular events that are involved in the release of neurotransmitter from these important cells. To do this we use combination of electrophysiology and fluorescence imaging to study the properties of vesicle exocytosis, transport and capture. Specific Aim 1 is to determine the properties of vesicle fusion at ribbon sites and outlier locations. Specific Aim 2 will examine the role the ribbon plays in collecting and transporting vesicles to the membrane prior to exocytosis. Specific Aim 3 explores the role of specific ribbon proteins in exocytosis. Understanding ribbon function may provide clues to help understand diseases that specifically affect vision and hearing, such as Usher syndrome. In addition, the fundamental understanding of presynaptic processes in these specialized neurons will have broader implications for neuronal communication in general and thus, may contribute to our understanding of various aspects of mental health and neurological disorders.